Breast marker

ABSTRACT

Tissue markers, systems for marking tissue, and methods of using tissue markers. A tissue marker may have a body with a first surface and a second surface, a plurality of coupling sites, and a plurality of elongate members. The tissue marker may include a remotely visible material. The tissue marker may have a delivery configuration that is different from a deployed configuration.

PRIORITY

This application is a U.S. nation phase of International Application No.PCT/US2007/081399, filed Oct. 15, 2007, which claims the benefit ofpriority to U.S. Provisional Patent Application No. 60/853,633, filedOct. 23, 2006, which is incorporated by reference into this applicationas if fully set forth herein.

BACKGROUND

It is often desirable to mark tissue with a marker so that it can laterbe identified. For example, tissue may be sampled by performing a biopsyto remove a small portion of the tissue. If the biopsy site is marked,the marker may later be used to guide a doctor or health careprofessional in returning to the site of the biopsy, should furthermedical procedures need to be performed at this site. For example,tissue (including small masses or microcalcifications) is sometimescompletely removed by procedures such as stereotactic core biopsy. Oftenduring these procedures, a metal clip is employed through the biopsyneedle to mark the target. Should another procedure be required in thesame area (e.g. a further excision or biopsy), the metal clip acts as amarker to aid in re-identification of the target or target region. Themarker may also be used to confirm that the biopsied site matches theintended target.

Unfortunately, there are many problems with currently available markerssuch as the metal clips mentioned above. In particular, markers such asmetal clips may move (or migrate) from the correct or initial position.Furthermore, the size and shape of these metal clips or other markers islimited because they must typically fit within the small diameter of adelivery needle. Finally, there may be problems identifying the markeronce it has been inserted.

Migration of tissue markers is a well-described phenomenon, which cancause serious problems with patient treatment. Migration may occurimmediately after insertion, or it may occur some time after insertion,and may have many causes. One common cause of clip migration occurs whenthe tissue (e.g., breast tissue) re-expands after compression orpressure on the tissue is released, for example, when the biopsyprocedure is completed. This may be referred to as the “accordioneffect.” Markers may also be displaced after being inserted into thetissue by formation of a hematoma, because the marker (particularlysmaller markers) may “float” within the hematoma.

Most currently available tissue markers are also limited tovisualization (or localization) by a single imaging modality. Forexample, metal clip markers may be radioopaque and therefore visible byX-ray based modalities, but may not be visualized by ultrasound or othermodalities. Furthermore, imaging of a tissue marker may also be limitedby the size or shape of the marker, because the size and shape of mostcurrently available markers are constrained by the insertion mechanism.For example, markers that are inserted through a biopsy needle generallyhave a cross-sectional dimension that is smaller than the diameter ofthe biopsy needle even after they have been inserted into the body.

Exemplary tissue markers have been described in U.S. Pat. No. 6,228,055to Foerster et al., U.S. Pat. No. 6,261,243 to Burney et al., U.S. Pat.No. 6,350,244 to Fisher, U.S. Pat. No. 6,234,177 to Barsch, and U.S.Pat. No. 6,371,904 to Sirimanne et al. Each of these references isincorporated in its entirety herein. However, none of these devicesadequately addresses all of the concerns described above.

Applicants have recognized that it would be desirable to provide arelatively large tissue marker that is deliverable in a smaller profilesheath, embodiments of which are described herein along with methods ofmaking same.

SUMMARY

Described herein are tissue markers, systems for marking tissue, andmethods of using tissue markers. In general, any of the tissue markersdescribed herein may be used to mark any appropriate tissue, includingbreast tissue.

Accordingly, in one embodiment, a tissue marker includes a body with afirst surface and a second surface and a plurality of coupling sites.The tissue marker also includes a plurality of elongate members. Atleast one of the body and/or one or more of the elongate membersincludes a remotely visible material. The first and second surfaces eachhave a minor diameter and a major diameter, and the major diameter islarger than the minor diameter. Each elongate member extends from acoupling site on at least one of the first and second surfaces. One ormore of the elongate members are configured to be positioned withrespect to the body in a delivery configuration and a deployedconfiguration. The deployed configuration is different from the deliveryconfiguration.

Also described herein are delivery systems. In one embodiment, adelivery system includes a sheath having a lumen, a pusher elementdisposed in the lumen, and a tissue marker disposed in the lumen distalof the pusher element. The tissue marker includes a body having a firstsurface and a second surface and a plurality of coupling sites. Thetissue marker also includes a plurality of elongate members, and atleast one of the body and/or one or more of the elongate membersincludes a remotely visible material. The first and second surfaces eachhave a minor diameter and a major diameter. The major diameter is largerthan the minor diameter. Each elongate member extends from a couplingsite on at least one of the first and second surfaces. One or more ofthe elongate members is configured to be positioned with respect to thebody in a delivery configuration and a deployed configuration; thedeployed configured is different from the delivery configuration.

Also described herein are methods of delivering a tissue marker to atissue site. In one embodiment, the method includes inserting a sheath(having a tissue marker disposed in a delivery configuration therein)into a tissue site, and releasing the tissue marker from the sheath. Thetissue marker may have a body including a first surface and a secondsurface and a plurality of coupling sites, and a plurality of elongatemembers, where each elongate member extending from a coupling site on atleast one of the first and second surfaces. The first and secondsurfaces may have a minor diameter and a major diameter (where the majordiameter is larger than the minor diameter). One or more of the elongatemembers may be configured to be positioned with respect to the body in adelivery configuration and a deployed configuration, where the deployedconfiguration is different from the delivery configuration. At least oneof the body and/or one or more of the elongate members includes aremotely visible material.

These and other embodiments, features and advantages will become moreapparent to those skilled in the art when taken with reference to thefollowing more detailed description of the invention in conjunction withthe accompanying drawings that are first briefly described.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B are perspective and side views of one embodiment of atissue marker.

FIGS. 2A-2C are perspective views of various exemplary tissue markerbody regions.

FIG. 2D is a top view of the body region of FIG. 2A.

FIG. 3A is a transparent perspective view of one embodiment of a bodyregion of a tissue marker.

FIG. 3B is a top view of one embodiment of a body region of a tissuemarker.

FIG. 4 is a partial view of a tissue marker near a coupling site.

FIG. 5 is a perspective view of another embodiment of a tissue marker.

FIGS. 6A and 6B are side views of a tissue marker in a deliveryconfiguration and a deployed configuration, respectively.

FIG. 7 is a side view of one embodiment of a tissue maker deliverysystem.

DETAILED DESCRIPTION

The following detailed description should be read with reference to thedrawings, in which like elements in different drawings are identicallynumbered. The drawings, which are not necessarily to scale, depictselected embodiments and are not intended to limit the scope of theinvention. The detailed description illustrates by way of example, notby way of limitation, the principles of the invention. This descriptionwill clearly enable one skilled in the art to make and use theinvention, and describes several embodiments, adaptations, variations,alternatives and uses of the invention, including what is presentlybelieved to be the best mode of carrying out the invention.

As used herein, the terms “about” or “approximately” for any numericalvalues or ranges indicate a suitable dimensional tolerance that allowsthe part or collection of components to function for its intendedpurpose as described herein. Also, as used herein, the terms “patient”,“host” and “subject” refer to any human or animal subject and are notintended to limit the systems or methods to human use, although use ofthe subject invention in a human patient represents a preferredembodiment.

The tissue marker described herein may include one or more members orregions (e.g., body region, elongate members, coupling sites) made of abioabsorbable/bioresorbable material. One suitable bioabsorbablematerial can be one or more of a metal alloy shown and described in U.S.Pat. No. 6,287,332, or the metal alloy shown and described in U.S.Patent Application Publication No. 2002/0004060, each of which isincorporated by reference in its entirety into this application.Preferably, the metallic bioabsorbable material is selected from a firstgroup consisting essentially of: magnesium, titanium, zirconium,niobium, tantalum, zinc, silicon, and combinations thereof. Alsoprovided are mixtures and alloys of metallic bioabsorbable materials,including those selected from the first group. Various alloys of thematerials in the first group can also be used as a metallicbioabsorbable material, such as a zinc-titanium alloy, for example, asdiscussed in U.S. Pat. No. 6,287,332 to Bolz et al., which isincorporated by reference in its entirety into this application. Thephysical properties of the alloy can be controlled by selecting themetallic bioabsorbable material, or forming alloys of two or moremetallic bioabsorbable materials. For example, the percentage by weightof titanium can be in the range of about 0.1% to about 1%, which canreduce the brittle quality of crystalline zinc. Without being bound totheory, it is believed that the addition of titanium leads to theformation of a Zn15 Ti phase. In another embodiment, gold can be addedto the zinc-titanium alloy at a percentage by weight of about 0.1% toabout 2%, which is believed to result in a further reduction of thegrain size when the material cures and further improving the tensilestrength of the material.

In some embodiments, the metallic bioabsorbable material can be an alloyof materials from the first group and a material selected from a secondgroup consisting essentially of: lithium, sodium, potassium, calcium,iron, manganese, and combinations thereof. The metallic bioabsorbablematerial from the first group can form a protective oxide or passivationcoating upon exposure to blood or interstitial fluid. The material fromthe second group is preferably soluble in blood or interstitial fluid topromote the dissolution of the oxide coating. Also provided are mixturesand alloys of metallic bioabsorbable materials, including those selectedfrom the second group and combinations of materials from the first groupand the second group.

Briefly, the combination of metal materials can be a metal alloy, theselection of the alloy constituents (as explained in detail below)serving to attain the prerequisite of biocompatible decomposition.Consequently, the metal alloy may consist of a combination of materialthat will decompose in the body comparatively rapidly while formingharmless constituents. Such alloy may include a component A which coversitself with a protective oxide coating. This component A is selectedfrom one or several metals of the group of magnesium, titanium,zirconium, niobium, tantalum, zinc, silicon, or combinations thereof.For uniform dissolution of the mentioned oxide coat to be attained, acomponent B is added to the alloy, possessing sufficient solubility inblood or interstitial fluid, such as lithium sodium, potassium, calcium,iron or manganese. The corrosion rate is adjusted by way of thecomposition so that gases, such as hydrogen, which evolve during thecorrosion of lithium, sodium, potassium, magnesium, calcium or zinc,dissolve physically and essentially not forming any macroscopic gasbubbles. Other alloys can be utilized such as, for example, alloy oflithium and magnesium in the ratio of about 60:40; a sodium-magnesiumalloy; a zinc-titanium alloy—the percentage by weight of which is in therange of about 0.1% to about 1% with the gold being optionally added ata percentage by weight of about 0.1% to about 2%. Further detailsrelating to these metallic bioabsorbable materials are found in U.S.Pat. No. 6,287,332 to Bolz et al.

Other materials for one or more members of the tissue marker asdescribed herein can include biodegradable polymers including shapememory polymers, such as, for example, polylactic acid, i.e., PLA,polyglycolic acid, i.e., PGA, polydioxanone, i.e., PDS,polyhydroxybutyrate, i.e., PHB, polyhydroxyvalerate, i.e., PHV andcopolymers or a combination of PHB and PHV (available commercially asBiopol®), polycaprolactone (available as Capronor®), polyanhydrides(aliphatic polyanhydrides in the back bone or side chains or aromaticpolyanhydrides with benzene in the side chain), polyorthoesters,polyaminoacids (e.g., poly-L-lysine, polyglutamic acid),pseudo-polyaminoacids (e.g., with back bone of polyaminoacids altered),polycyanocrylates, or polyphosphazenes.

As used herein, the term “bioresorbable” or “bioabsorbable” includes asuitable biocompatible material, mixture of materials or partialcomponents of materials being degraded into other generally non-toxicmaterials by an agent present in biological tissue (i.e., beingbio-degradable via a suitable mechanism, such as, for example,hydrolysis) or being removed by cellular activity (i.e., bioresorption,bioabsorption, or bioresorbable), by bulk or surface degradation (i.e.,bioerosion such as, for example, by utilizing a water insoluble polymerthat is soluble in water upon contact with biological tissue or fluid),or a combination of one or more of the biodegradable, bioerodable, orbioresorbable material noted above.

As mentioned above, the tissue markers described herein may be used tomark any appropriate tissue. In particular, the tissue marker may beconfigured as a breast tissue marker. For the sake of convenience, thedescription provided below is sectioned into a description of tissuemarkers (including breast tissue markers), inserters for inserting atissue markers (including systems for inserting tissue markers), andmethods of inserting and visualizing these tissue markers. Featuresincluded in the description from any of the sections below may beapplied to any of the other sections. For example, features of thetissue markers described herein may be applied to the systems andmethods for using such tissue markers.

In general, the tissue markers described herein include a body havingone or more coupling sites that couple to one or more elongate members.At least one region of either the body and/or one or more elongatemember may include a remotely visible material that aids invisualization of the tissue marker. The tissue marker, and particularlyan elongate member of the tissue marker, may include one or moreattachment members configured to help secure the marker in the tissue.The tissue marker generally has a delivery configuration and a deployedconfiguration, and may change from the delivery configuration (eitherautomatically or by some active mechanism) into the deployedconfiguration after being inserted into a target tissue site.

FIGS. 1A and 1B illustrate one embodiment of a tissue marker. FIG. 1Ashows a perspective view of a tissue marker. This tissue marker includesa body 101 (also referred to as a body region) and a plurality ofelongate members 103 attached to the body region through attachmentmembers 105. The body, elongate members, and attachment region aredescribed more fully below. FIG. 1B shows a side view of the tissuemarker shown in FIG. 1A.

The body of the tissue marker may form the core region of the marker. Insome embodiments the body is a constant shape. In other embodiments, thebody may change shape (e.g., between a deployed and a deliveryconfiguration). The body of the tissue markers described herein may haveany appropriate shape, but particularly shapes having at least a firstsurface and a second surface, where the first and second surfaces have amajor diameter and a minor diameter. As used herein, the “surfaces” ofthe body may be any appropriate surfaces. For example a surface of thebody of the tissue marker may include flat or curved surfaces, andinclude smooth or irregular (e.g., rough) surfaces, continuous orinterrupted surfaces, stiff or flexible surfaces, or the like. As usedherein, the term “diameter” may mean the distance across a surface. Adiameter, including a major or minor diameter, may be measured across asurface in a straight or a curved line. In general, the major diameterof a surface is the largest diameter across the surface, and the minordiameter of the surface is the smallest diameter measured across thesurface. The major diameter of the surface of a tissue marker istypically larger than the minor diameter of the surface off a tissuemarker. For example, in one embodiment, the length of the major diametermay be approximately 1.1×, 1.2×, 1.5×, 2×, 3×, 4×, 5×, 10×, etc. thelength of the minor diameter. In some embodiments, the major and minordiameter may be approximately equivalent to one another. Although thethree-dimensional shape of a surface of the tissue marker body maychange (e.g., the tissue marker body may bend or flex), the major and/orminor diameters may remain relatively the same. In some embodiments, themajor and minor diameter of the tissue marker body may change.

As mentioned, a surface of the body of the breast marker may be planar(e.g., flat) or curved. The surface may be generally oval, triangular,rectangular, polyhedral, or some combination of these shapes. Ingeneral, the body of the breast measurement device comprises at leasttwo surfaces which may connect to each other directly (e.g., at an edge)or may be connected via one or more side walls. For example, the body ofa breast marker may have a generally flattened oval shape having a first(e.g., upper) surface and a second (e.g., lower) surface. In someembodiments the first and second surfaces do not meet at a defined edge.

In general, the body of the breast marker includes at least twosurfaces, and these surfaces may be part of the overall structure of thebreast marker body. For example, the body a may be generally flattened(e.g., disk-shaped or the like), or rounded. In some embodiments, thebody may be flexible so that the shape of the body may change. Forexample, the body may have an expanded or relaxed deployed configurationand a compressed delivery configuration. In one embodiment, at least aportion of the body is made of a flexible material that can be bent topermit the body or tissue marker to assume a delivery configuration thathas a smaller profile than a relaxed (unbent) or deployed configuration,as described in further detail below. Although many of the embodimentsof the tissue marker body described herein are solid shapes, othershapes may be useful as body shapes. For example, the body may be ascaffold, or may include connecting regions that help connect differentregions of the body.

The body of the tissue marker may be made of any appropriate material,or combination of materials, particularly including the metal andpolymeric materials (e.g., the bioabsorbable/bioresorbable material)described above. The body may be made of a single material orcombination of materials, or it may have different regions that comprisedifferent materials. In some embodiments, one or more surfaces of thetissue marker body may be coated or partially coated with a materialthat aids in delivery of the device. For example, the body may have alubricious coating. Other coatings may include bioactive coatings (e.g.,drug eluting coatings, coatings to encourage or inhibit tissue ingrowth,or the like), visualization coatings (e.g., radiopaque coatings,florescent coatings, etc.), protective coatings (e.g., wax coatings,polymeric coatings, etc.). The tissue marker body may also includeregions comprising materials that are bioactive (e.g., configured to bereleased from the tissue marker over time), or for visualization. Forexample, the tissue marker may include one or more internal regions(e.g., a core) made of any material that may be visualized remotely,after the tissue marker has been implanted in to body, or to helpvisualize the tissue marker after it has been implanted.

FIGS. 2A-2C illustrate different exemplary tissue marker bodies. Theexemplary body region shown in FIG. 2A has a first (upper) surface 202and a second (lower) surface (not visible in FIG. 2A). A side wallregion 205 connects the first and second surface. The first and secondsurface are both oval in shape, as can be seen in FIG. 2D, which shows atop view of this embodiment of a tissue marker body region. In FIG. 2A,the perimeter of the first and second surfaces both form oval shapes. Inother variations, the perimeter of these surfaces may have differentshapes. Furthermore, the first and second surfaces may also havedifferent contours. For example, the first surface may be planar (flat)and the second surface may be curved. The first 202 and second surfacesof the body region in FIG. 2A are separated from each other by thethickness of the side wall 205. The side wall may be any appropriatethickness, though in some embodiments, the side wall is thin, or absent.In some variations, the side wall material is approximately 0.025 mm to3 mm thick, allowing an 8G biopsy needle (having an inner diameter ofapproximately 3.4 mm) to fit inside. For example, the embodiment of thebody region of a tissue marker shown in FIG. 2B comprises only a firstand second surface, and does not include an additional side wallsurface.

In FIG. 2B, the first 212 and second 213 surfaces are both shown ascurved surfaces, and the perimeter of these surfaces meet to form anedge 217. In FIG. 2B the perimeter of the first 212 and second 213surfaces form an oval having a major (long) and a minor (short) axis. Asmentioned, the first and second surfaces may have any appropriate shape.For example, FIG. 2C shows an example of a body region having a first232 and second surface that are rectangular, with a major (e.g., long)axis and a minor (e.g., short) axis. The rectangular surfaces of FIG. 2Care generally parallel and are separated from each other by a side wall215.

The first and second surfaces may have any appropriate dimensions,although they generally include a major diameter and a minor diameter,as mentioned. FIG. 2D shows a top view of the body region shown in FIG.2A. Lines 224 and 225 indicate the major, or long, axis and the minor,or short, axis. The major axis is generally longer than the minor axis,as mentioned above. Although all of the examples shown herein have bodyregions with first and second surfaces that are substantially parallel,the first and second surfaces may also be non-parallel, includingperpendicular surfaces. In some variations, the minor diameter isbetween about 2 mm to about 3 mm. In some variations, the major diameteris between about 2 mm to about 15 mm

Elongate members are generally coupled to the body of the tissue markerthough one or more coupling sites. A coupling site links one or moreelongate members to the body of the tissue marker, and the elongatemember may be movably or rigidly coupled. Any appropriate coupling sitemay be used. A coupling site may be present on any part of the bodyregion, such as the first and/or second surfaces, or the sidewall. Insome embodiments, a coupling site is present on the first surface. Forexample a coupling site may be a mount that is attached to the firstsurface into which an elongate member is received. In some embodiments,the coupling site is a pit or socket in a surface of the body into whichthe elongate member engages. In other embodiments, a coupling sitecomprises a hole passing through (or in communication with) two or moresurfaces of the body region. In this embodiment, an elongate member maypass completely through the coupling site, and the elongate member mayproject from both the first and the second surfaces of the body of thetissue marker.

As mentioned, a coupling site may movably couple the elongate member tothe body region of the tissue marker. For example, a coupling site mayattach to an elongate member so that the elongate member can bend, slideand/or twist with respect to the body region of the tissue marker. Insome embodiments, the coupling site includes one or more hinges thatpermit an elongate member to move. For example, one or more elongateregions may be attached to a hinge portion of a coupling site, and acomplementary portion of the hinge maybe attached to the body,permitting the elongate member to move with respect to the body. Thecoupling site may also include a pin or lock to secure the elongatemember within the coupling site and prevent or inhibit movement. In someembodiments, the coupling site may include a shape-memory mount tocouple one or more elongate members to a surface of the body of thetissue marker. In this embodiment the position of the elongate memberwith respect to the body region maybe changed based on the configurationof the shape-memory alloy.

Returning now to FIGS. 1A and 1B, coupling sites 105 are shown as holespassing thought the aligned first and second surfaces of the body region101. Thus, elongate members 103 project through the body region 101 bypassing through the coupling sites 105. Although a single elongatemember 103 is shown linked to a single coupling site, it should beunderstood that multiple elongate members may be linked to a singlecoupling site. Although a coupling site may permit movement of anelongate member relative to the body region, coupling sites typicallyprevent the elongate member from de-coupling with the body region (e.g.,and separate from the tissue marker). In the embodiment shown in FIGS.1A and 1B, the elongate member is fixed to the body region of the tissuemarker. For example, an elongate member may be friction fit within thebody region. An adhesive, pin, clamp, or holdfast may be used to securean elongate member within a coupling site. In some embodiments, thecoupling site comprises a threaded portion into which an elongate memberscrews. A coupling site may also movably couple an elongate member to abody region. For example, a coupling site may comprise a hinge, axel,pin, track, or the like, through which an elongate member may move.

The exemplary body regions shown in FIGS. 2A-2D also include couplingsites 220. In FIGS. 2A-2D, these coupling sites are shown as holesthrough the first and second surfaces of the body region. As mentionedabove, a coupling site is not limited to a hole or passage through thebody region of the tissue marker. For example, a coupling site may be amount that attaches to the body region and projects from a surface tocouple to an elongate member. Of course a mount may also be recessedwithin the surface (or partly within the surface). In some embodiments,the coupling site includes a region that mates with at least one regionof an elongate member. For example, the coupling site may include a maleregion (e.g., a pin, axel, hinge, pivot, etc.) that mates with a femaleregion (e.g., hole, groove, pit, etc.) on the elongate member, or afemale region of the coupling site may mate with a male region of theelongate member.

Although the majority of examples of coupling sites provided hereindescribe mostly mechanical couplings, a coupling site may alsonon-mechanically couple an elongate member to the body of the tissuemarker. For example, the coupling site may magnetically couple one ormore elongate members to the body of the tissue marker. In someembodiments, the coupling site includes both mechanical and electricaland/or magnetic components.

FIG. 3A shows one embodiment of a coupling site 220 comprising apassageway through the body of a tissue marker. Three coupling sites areshown in FIG. 3A. Each coupling site extends from a first (e.g., upper)surface 302 of the body of the tissue marker through the body, and to asecond (e.g., lower) surface 304 that is aligned with the first surface.The coupling site has an inner wall with a convex profile as it passesfrom the first to the second surface. An elongate member may be securedwithin the coupling site by having a narrow diameter region (surroundedby wider diameter regions) on its length that fits through theconstricted inner region of the coupling site. In this example, theprofile of the passageway of the coupling site may allow an elongatemember to pivot within the coupling site with respect to the body regionof the tissue marker.

In some embodiments, the coupling site also includes one or more jointmembers. A joint member may help secure an elongate member to thecoupling site. In some embodiments, the joint member is an elastomericor compressible material that permits the elongate member to move withrespect to the body. Examples of elastomeric materials may include (butare not limited to) silicones, latex, rubbers, thermoplastic elastomers(TPE's) such as styrene-ethylene/butylene-styrene block copolymers(SEBS)-based TPE's (such as C-Flex), polysiloxane modified SEBS andtheir associated families, polyvinylchloride (PVC), cross-linkedpolyolefins such as polyethylene, and various polyurethanes. Elastomericmaterials may also be compressible materials, and may also includefoams, gels, and the like.

FIG. 3B shows a body region of a tissue marker having five couplingsites 220. Each coupling site 220 includes a joint member 301. In thisexample, the coupling site includes a passage between two surfaces ofthe body of the tissue marker. This passage has an oval cross-section,and the joint member abuts the walls of the passage, and forms apassageway through the body into which an elongate member may pass. Inthis embodiment, the coupling site and is configured so that an elongatemember coupled to the coupling site can move (e.g., relative to thebody) preferentially in one direction. In particular, an elongate memberpassing though the coupling site 220 can move preferentially in thedirection formed by the long axis of the elliptical cross-section of thecoupling site. In operation, the elongate member couple compresses thejoint member against the body, since the joint member is at leastsomewhat compressible.

FIG. 4 illustrates one embodiment of a coupling site 220, showing anelongate member 401 coupled to a portion of a body region 420 of atissue marker. The coupling region show in FIG. 4 includes a jointmember 403. In this embodiment the coupling site 220 forms a passagewaythrough the body between the first surface 440 and the second surface450. The coupling site is shown as a circular passageway, lined by ajoint member. The joint member 403 is an elastomeric material betweenthe body region of the tissue marker and the elongate member 401. Thus,the elongate member may bend with respect to the body region bycompressing the joint member 403, as indicated by the arrows 425, 425′.

In general, a coupling site may be located in any appropriate portion ofthe body of a tissue marker, and any appropriate number of couplingsites could be used. For example, in FIG. 3B, five coupling sites areshown, and these coupling sites are located along the periphery of thebody as well as through a central region. In FIG. 3B, the coupling sitesextend through the aligned (e.g., approximately parallel) first andsecond surfaces of the body of the tissue marker. As mentioned above,the coupling site may couple and elongate member to only one surface(e.g., the first or second surface) of the body region. Thus, couplingsites may not be symmetrically arranged across the body of the tissuemarker.

One or more elongate members typically extend from the body region ofthe tissue marker and are coupled to the body region through couplingsites. An elongate member may have any appropriate length, curvature andcross-section. For example, the elongate member may have a circularcross-section, a tear-drop cross section, and oval cross-section, apolyhedral cross-section, or some combination thereof. In someembodiments the elongate member is bifurcated (e.g., branches). Anelongate member may be straight or curved, and may have a uniformcross-section along its length, or the cross section may vary along thelength. In some embodiments, the elongate member tapers as it extendsfrom the body of the tissue marker. The elongate member may be solid,porous, tubular, or some combination thereof. As described above, anelongate member may be made of any appropriate material, preferablybiocompatible materials including metals, polymers, ceramics, or somecombination of materials. In addition, an elongate member may alsoinclude one or more bioactive materials (e.g., drugs, enzymes, etc),including bioactive materials to aid in wound healing, tissue ingrowth,or the like. Finally, as described in more detail below, the elongatemembers may include a material to help aid in visualizing the tissuemarker.

Although many of the examples shown herein describe tissue markershaving a plurality of elongate members, a tissue marker may have anynumber of elongate members, including a single elongate member. In somevariations, the tissue marker includes more than one elongate member(e.g., 2, 3, 4, 5, 6, 7, etc.). As described herein, a single elongatemember may extend through the body region and project from both sides,or the body region may include two or more elongate members that extendfrom the body region (and appear to pass through the body region).

Returning now to the tissue marker 100 shown in FIGS. 1A and 1B, fourelongate members 103 are shown extending from the body region 101. Inthis embodiment the elongate member extends symmetrically from the bodyregion by passing through the body so that they project from both thefirst and second surfaces. The elongate members 103 are shown as curved,extending generally away from the body region 101 in this (e.g.,deployed) configuration. Thus, each elongate member is shown as a curvedcylindrical member having a tapered distal end. In other embodiments,the elongate members do not pass through the body of the tissue marker,but may project only from one side, or do not symmetrically project fromthe body region.

An elongate member may also include one or more tissue engagementregions or attachment members. Examples of different attachment membersinclude hooks, loops, suckers, barbs, pores, and the like. Attachmentmembers may be located along any portion of the elongate member and mayhelp secure the tissue marker in the tissue. In some embodiments,attachment members are located at a distal portion of the elongatemember (e.g., distal from the body region). More than one attachmentmember may be present on an elongate member. For example, in oneembodiment an elongate member includes attachment members configured asbarbs along the length of the elongate member, extending from the bodyregion of the tissue marker to the distal tip. In one variation, theattachment member is a hook. For example, the elongate member may have ahook at its distal end.

FIG. 5 shows another embodiment of a tissue marker 500 having elongatemembers 501 with attachment members 503 (shown here as barbs) at thedistal ends of each elongate member. The elongate members 501 in FIG. 5are also curved; however it should be understood that (in general)elongate members may be straight, or bent instead of (or in addition to)being curved. Furthermore, the direction of any curve or bend may bedifferent from that shown in FIGS. 1A, 1B and 5. For example, in someembodiments, the elongate members curve or bend inwards. In someembodiments, the elongate members may extend in a generally firstdirection and then in a different generally second direction.

A tissue marker may include more than one elongate member, and any ofthe elongate members included as part of the tissue marker may havedifferent properties. For example, different elongate members of atissue marker may have different lengths or curvatures. Furthermore, asmentioned above, the position and relationship of the elongate memberswith respect to the body region of the tissue marker may be configuredto change. For example, the elongate members may be configured to bendwith respect to the body region.

As previously described, a coupling site may allow an elongate member tomove with respect to the body region. Furthermore, an elongate membermay itself bend or flex. In some embodiments, the elongate member ismade of a material that permits such movement. For example, the elongatemember may be made of a material that permits it to change shape from aan initial configuration (and preferably later to return to the initialconfiguration). Thus, the elongate member may be made (at least in part)of a shape-memory alloy, or an elastomeric material, or the like. Insome embodiments the elongate member comprises a hinged joint region.

The tissue markers described herein may therefore have more then oneconfiguration, including a deployed configuration and a deliveryconfiguration. In general a deployed configuration is the configurationthat a tissue marker assumes when it is relaxed (e.g., when there are nosubstantial net forces acting upon the tissue marker or regions of thetissue marker) and/or when the tissue marker is released into a tissue.A delivery configuration is the configuration that the device assumeswhen the tissue marker is compressed into a smaller-profile shape (e.g.,for insertion into tissue). Typically, the deployed configuration of atissue marker allows engagement of the tissue marker with anysurrounding tissue. Thus, in a deployed configuration the elongatedmembers of a tissue marker are expanded, extending from the centralregion of the tissue marker (in some embodiments, the body region of themarker) to stably contact tissue.

A tissue marker may have multiple delivery and/or deployedconfigurations, since there may be numerous ways to configure (and/orcompress) any particular tissue marker. In some embodiments, the tissuemarker is configured to be inserted into tissue through a tubular (e.g.,needle) inserter, and therefore the delivery configuration is compatiblewith a tubular inserter. As described briefly above, any region of thetissue marker, including the elongate members and body region, may beconfigured to change shape from a deployed configuration into deliveryconfiguration (and vice versa). For example, the body of the tissuemarker may be configured to bend or curl and more readily fit within acannula, catheter, sheath or other device utilized for delivery. In someembodiments, the tissue marker may be compressed from a deployedconfiguration into a delivery configuration. A tissue marker may alsohave more than one delivery configuration, or more than one deployedconfiguration. In some embodiments, the tissue marker changes between adelivery and a deployed configuration by moving the elongate memberswith respect to the body. The in some embodiments, the body region doesnot substantially change shape. For example, the elongate members maybend (or the coupling sites to which they are attached may move), whilethe body remains relatively fixed.

FIGS. 6A and 6B illustrate a tissue marker in a delivery and a deployedconfiguration, respectively. In FIG. 6A the tissue marker is shown in adelivery configuration within a cannula 601. In this example, theelongate members 640 extend approximately parallel to the walls of thecannula 601, and the body region 635 is angled so that it more easilyfits within the cannula. The body region 635 in this example isgenerally longer than it is wide (e.g., it forms an oval or rectangularshape having a first and second surface each with a major diameter thatis larger than a minor diameter), so that tilting the body region maypass through the opening of the cannula. The cannula may be part of astorage or delivery device (as described in detail below). In FIG. 6B,the tissue marker is shown in a deployed configuration, in which thelegs 640 extend fully from each other and from the body region 635.

A tissue marker may be implanted into a tissue so that it can bevisualized within and mark a location within the tissue. Thus, any ofthe tissue markers described herein may include one or more remotelyvisible materials allowing them to be visualized once they have beeninserted into the tissue. In some embodiments, the shape or texture ofall or a portion of the tissue marker may aid in remotely visualizingthe marker. Furthermore, in some embodiments, the tissue marker mayinclude an active signaling component for transmitting a signal from thetissue marker to a remote receiving device. Examples of methods ofremotely visualizing a tissue marker may include (but are not limitedto) x-ray based scanning techniques (e.g., fluoroscopy, angiography, CTScanning, etc.), radiation-based scanning (e.g., PET/SPCT, NMR),magnetic-based scanning (MRI), sound-based scanning techniques (e.g.,ultrasound), and the like.

For example, in some embodiments all or a portion of the tissue markermay include a radiopaque material that is remotely visible (e.g.,particularly during x-ray or radiation-based scans). Radiopaquematerials are well-known, and include many biocompatible metals,compounds and polymers. For example, metals such as gold, titanium, andcompounds containing barium sulfate, bismuth, and tungsten have all beenused as radiopaque materials. In some embodiments, all or a portion ofthe tissue marker may include a ferromagnetic or paramagnetic material(e.g., an iron oxide), that is visible using magnetic-based scanning(e.g., MRI). In some embodiments, the tissue marker comprises anon-ferromagnetic metal or material that is MRI compatible. Materialshaving a high ultrasound reflectivity may generally be visualized usingultrasound. Materials having a high contrast of acoustic impedancereflect and scatter ultrasonic energy. An example of such a materialincludes a material having gas-filled internal pores, or other materialshaving regions of discontinuous acoustic reflectivity.

Many of the tissue markers described herein may be visualized using morethan one visualization modality. Thus, a single tissue marker mayinclude more than one remotely visible material, or a remotely visiblematerial that can be visualized under different modalities (for example,a material that is both radiopaque and ferromagnetic). Furthermore, anactive signaling component may also be included as part of the tissuemarker to transmit a signal from the tissue marker to be detected by aremote receiving device. For example, the tissue marker may include aminiaturized RF transmitter, a piezoelectric transmitter, or othersignal transmitter. The signal may act as a beacon (e.g., indicatinglocation) or may encode information about the surroundings or status ofthe tissue marker.

In general, a remotely visible material may be included in any portionof the tissue marker. For example, the remotely visible material may beincluded in the body (or a portion of the body) of the marker, or in oneor more of the elongated members coupled to the body or in a couplingsite or in a region attached to one of these sites. In some embodiments,the entire tissue marker is remotely visible under one or more of themodalities described above.

Any of the tissue markers described herein may be inserted into tissueusing a delivery device or system. In general, a delivery deviceincludes a sheath in which the tissue marker may be positioned. Asdescribed briefly above, the tissue marker can be positioned within thesheath or other region of the delivery device in a deliveryconfiguration. The delivery device may also include a delivery actuatorfor controllably propelling the tissue marker from the sheath and into atissue. Thus, a delivery system may include a delivery device (includinga sheath and a delivery actuator) and one or more tissue markers. Thetissue marker is preferably pre-loaded into the sheath of the deliverydevice. The sheath of a delivery device may be, for example, a cannula,or a region connectable to a cannula. In some embodiments, a tube orcannula is preferred, because it can be readily inserted into tissuebefore releasing the marker into the tissue. For example, the deliverydevice may be part of a biopsy needle, or may be used in conjunctionwith a biopsy needle. The tissue marker may then be pre-loaded into thelumen of the cannula so that it can be expelled through the lumen andinto the tissue. In some embodiments, the delivery actuator is also incommunication with the lumen of the cannula where the tissue marker hasbeen loaded.

FIG. 7 shows one embodiment of a tissue maker delivery system. In FIG. 7a sheath (shown as a tube or cannula) 703 is loaded with a tissue marker701 in a delivery configuration, and a delivery actuator (shown as apusher element 705) is positioned to push the tissue marker through thelumen of the sheath and into the tissue. The pusher element 705 in thisexample is configured as a piston, having a piston head 707, and apiston arm 709, and is shown immediately distal to the loaded tissuemarker. In general, a pusher element may be any physical actuatorconfigured to push a tissue marker from the sheath. When the distal endof the sheath has been positioned appropriately for delivery of thetissue marker, the piston arm portion of the pusher element may be movedto expel the tissue marker from the sheath. Thus, the pusher element maybe manipulated by a medical professional acting from the proximal (e.g.,external) end of the delivery device and thereby implant the tissuemarker. Pushing the pusher element distally may cause the piston head topush the tissue marker from the lumen of the sheath.

A delivery actuator typically acts to apply force to expel the tissuemarker from the sheath of the delivery device and into the tissue. Thus,the delivery actuator may push or pull the tissue marker from the sheathinto the tissue by any appropriate means. In addition to theplunger-type delivery actuator illustrated in FIG. 7, other types ofdelivery actuators may be used. Other examples of actuators includeother mechanical actuators (e.g., pullers, sliders, etc.), pneumatic orhydraulic (e.g. pressure) actuators, magnetic actuators, or the like.For example, a pneumatic or hydraulic actuator may act by inflating aballoon to expel a tissue marker.

The tissue markers and/or delivery systems described herein may also besterilized (or sterilizable) and packaged for use. In some embodiments,the tissue markers are packaged for single-use, in disposable sterilepackaging. An entire delivery system (including a sheath, pre-loadedtissue marker and actuator such as a pusher element) may therefore bepackaged for single use. In some embodiments, the delivery sheath andpusher element may be re-used with another tissue marker. The tissuemarker may also be packaged with instructions. In some embodiments themaker is coded with an identifier (e.g., a numeric, alphanumeric, barcode, etc.). The identifier may indicate the manufacturing date,location of manufacturing, patient or procedure information, or anyother appropriate information.

Although the delivery devices described above are well adapted for usewith the tissue markers described herein, it should be understood thatthey may be used with any appropriate tissue marker, and are not limitedto those described herein.

In operation, the tissue markers described herein may be inserted into atissue by inserting the tissue marker into the tissue in the deliveryconfiguration, and expelling the tissue marker from into the tissue sothat it assumes a deployed configuration. Thus, a tissue marker deliverysystem as described above may be used to implant a tissue marker.

For example, using a tissue marker delivery system such as that shown inFIG. 7, the sheath of the delivery system is loaded with a tissuemarker. The lumen of the delivery system sheath may be continuous withthe lumen of a cannula (e.g., needle). A doctor, or other medicalprofessional, typically positions the distal tip of this cannula withinthe tissue in the location where it is desirable to mark the tissue. Forexample, during a breast tissue biopsy, it may be desirable to mark thebreast tissue at the location where the biopsy occurred. After removinga biopsy (e.g., a portion of the breast tissue), the medicalprofessional positions the distal tip of a delivery device cannula atthe site of the biopsy (or adjacent to the site) and applies force toexpel the tissue marker from the sheath of the delivery device. In theembodiment described in FIG. 7, the medical professional pushes thepusher element so that the tissue marker is expelled. The tissue markerslides thorough the lumen of the sheath in the compressed deliveryconfiguration. Once it is released from the sheath, the tissue markerexpands into its deployed configuration, and embeds into the tissue.

In some embodiments, the conversion between the delivery and deployedconfiguration occurs because the internal energy (e.g., arising from thespring constant) stored by the tissue marker in the deliveryconfiguration. Thus, the energy stored by compressing the tissue implantis released by allowing the tissue marker to expand back into a deployedconfiguration, once the restraining force (e.g., from the walls of thesheath or cannula) on the device is lessened or released. In someembodiments, the change in configuration may be due to shape-memoryeffects resulting from a martensite transformation. This transformationmay be triggered by the change in temperature (e.g., raising thetemperature from the delivery device to body temperature) afterinserting the tissue marker into the tissue.

Multiple tissue markers may be inserted into the same site, or a singletissue marker may be inserted. Tissue markers may be inserted intodifferent regions (including adjacent regions). Although the insertionmethod described above is specific to insertion via a delivery devicehaving a cannula, it should be understood that other delivery devicesmay be used. For example, a catheter-based delivery device could also beused.

In some embodiments, multiple markers may be loaded in to the deliverysystem. Thus, the delivery system may be configured to hold and delivermultiple tissue markers. For example, markers may be loaded sequentiallyinto a delivery system or in parallel. When multiple tissue markers areloaded into a delivery system a single actuator may be used to deliveryone or more marker at a time. In some variations, multiple actuatorsloaded in parallel may be delivered by separate actuators. Anyappropriate number of actuators may be preloaded into a delivery system.Tissue markers may be tethered to each other. For example, tissuemarkers may be tethered to one or more other tissue markers by aflexible, biocompatible (and/or biodegradable) material, as describedabove. In one variation, tissue markers are tethered to each other usinga surgical suturing material (e.g., Poliglecaprone, Polyglactin,Polyglycolic acid, Polydioxanone, catgut, silk, polyester, stainlesssteel, polypropylene, polyethylene, etc.).

Once the device has been released into the tissue, the delivery cannulacan be removed from the tissue, and the tissue closed off to preventinfection or contamination. Because the tissue marker can be remotelyvisualized, the insertion procedure can be visualized (e.g., usingfluoroscopy or other visualization methods). Once the tissue marker hasbeen inserted, it can be repeatedly visualized remotely using anappropriate or compatible visualization method. Visualization of thetissue marker may be done using the standard methods for visualizingtissue by the appropriate visualization method.

This invention has been described and specific examples of the inventionhave been portrayed. While the invention has been described in terms ofparticular embodiments and illustrative figures, those of ordinary skillin the art will recognize that the invention is not limited to theembodiments or figures described. In addition, where methods and stepsdescribed above indicate certain events occurring in certain order,those of ordinary skill in the art will recognize that the ordering ofcertain steps may be modified and that such modifications are inaccordance with the variations of the invention. Additionally, certainof the steps may be performed concurrently in a parallel process whenpossible, as well as performed sequentially as described above.Therefore, to the extent there are variations of the invention, whichare within the spirit of the disclosure or equivalent to the inventionsfound in the claims, it is the intent that this patent will cover thosevariations as well. Finally, all publications and patent applicationscited in this specification are herein incorporated by reference intheir entirety as if each individual publication or patent applicationwere specifically and individually put forth herein.

1. A tissue marker, comprising: a body including a first surface and asecond surface, the first surface and the second surface beingoppositely facing, and the body having a plurality of coupling sites;and a plurality of elongate members, each elongate member of theplurality of elongate members extending from a respective coupling siteof the plurality of coupling sites to project outwardly from arespective surface of the first and second surfaces, one or more of theelongate members configured to be positioned with respect to the body ina delivery configuration and a deployed configuration different from thedelivery configuration, at least one of the body and one or more of theelongate members including a remotely visible material.
 2. (canceled) 3.(canceled)
 4. The tissue marker according to claim 1, wherein the firstsurface is separated from and generally parallel to the second surface.5. The tissue marker according to claim 1, wherein each of the firstsurface and the second surface has a minor diameter and a major diameterlarger than the minor diameter, and the first and second surfaces havesubstantially equivalent minor and major diameters.
 6. The tissue markeraccording to claim 5, wherein the first surface is generally parallel tothe second surface and the first and second surfaces are separated by aside wall.
 7. (canceled)
 8. (canceled)
 9. The tissue marker according toclaim 1, wherein the coupling sites comprise openings in the firstsurface aligned with openings in the second surface wherein the elongatemembers are disposed in the openings, and wherein each of the elongatemembers have a first end extending from the first surface and a secondend extending from the second surface, at least one of the first andsecond ends of one or more elongate members including an attachmentmember.
 10. (canceled)
 11. (canceled)
 12. The tissue marker according toclaim 9, wherein the attachment member comprises a hook, and wherein thehook is oriented toward a central longitudinal axis of the marker in thedelivery configuration.
 13. (canceled)
 14. (canceled)
 15. The tissuemarker according to claim 9, further comprising a joint member disposedin the openings, the elongate members coupled to the joint members. 16.(canceled)
 17. The tissue marker according to claim 1, wherein theelongate members are positioned generally perpendicular to the body inthe deployed configuration and generally oblique to the body in thedelivery configuration.
 18. The tissue marker according to claim 17,wherein the body is positioned generally oblique to a longitudinal axisof a delivery sheath in the delivery configuration.
 19. The tissuemarker according to claim 1, wherein one or more of the elongate membersincludes a shaft with a first radius of curvature.
 20. (canceled) 21.(canceled)
 22. (canceled)
 23. The tissue marker according to claim 1,wherein at least one of the elongate members is made of a materialdifferent from the material of another of the elongate members.
 24. Thetissue marker according to claim 1, wherein the elongate members aremade of essentially the same material, the body including a materialdifferent from the material of the elongate members.
 25. The tissuemarker according to claim 1, wherein one or more of the coupling sitesincludes a hinge.
 26. The tissue marker according to claim 1, whereinthe number of elongate members extending from the coupling sites on thefirst surface is different from the number of elongate members extendingfrom the coupling sites on the second surface.
 27. The tissue markeraccording to claim 1, wherein at least one of the first and secondsurfaces are curved.
 28. The tissue marker according to claim 27,wherein both first and second surfaces are curved, a circumferentialedge of the first surface connected to a circumferential edge of thesecond surface.
 29. A delivery system, comprising: a sheath including alumen; a pusher element disposed in the lumen; and a tissue markerdisposed in the lumen distal of the pusher element, the tissue markercomprising: a body including a first surface and a second surface, thefirst surface and the second surface being oppositely facing, and thebody having a plurality of coupling sites; and a plurality of elongatemembers, each elongate member of the plurality of elongate membersextending from a respective coupling site of the plurality of couplingsites to project outwardly from a respective surface of the first andsecond surfaces, one or more of the elongate members configured to bepositioned with respect to the body in a delivery configuration and adeployed configuration different from the delivery configuration, atleast one of the body and one or more of the elongate members includinga remotely visible material.
 30. (canceled)
 31. The tissue markeraccording to claim 29, wherein the elongate members are positionedgenerally perpendicular to the body in the deployed configuration andgenerally oblique to the body in the delivery configuration.
 32. Thetissue marker according to claim 31, wherein the body is positionedgenerally oblique to a longitudinal axis of the sheath in the deliveryconfiguration.
 33. (canceled)
 34. (canceled)
 35. (canceled) 36.(canceled)
 37. (canceled)
 38. (canceled)
 39. (canceled)
 40. A tissuemarker, comprising: a body having a disk-like shape, the body includinga first surface and a second surface, the first surface being separatedfrom the second surface along at least a portion of the body, the bodyhaving a plurality of coupling sites; and a plurality of elongatemembers, each elongate member of the plurality of elongate membersextending from a respective coupling site of the plurality of couplingsites to project outwardly from a respective surface of the first andsecond surfaces, and the plurality of elongate members being configuredto be positioned with respect to the body in a delivery configurationand a deployed configuration different from the delivery configuration.41. The tissue marker of claim 40, wherein each of the plurality ofelongate members is positioned generally perpendicular to the respectivesurface of the body in the deployed configuration and generally obliqueto the respective surface of the body in the delivery configuration. 42.The tissue marker according to claim 40, wherein a perimeter of thefirst surface and a perimeter of the second surface meet to form anedge.
 43. The tissue marker according to claim 40, wherein a side wallextends between a perimeter of the first surface and a perimeter of thesecond surface.
 44. The tissue marker according to claim 40, whereineach of the first surface and the second surface has a minor diameterand a major diameter larger than the minor diameter, the minor diametersof the first surface and the second surface being substantiallyequivalent and the major diameters of the first surface and the secondsurface being substantially equivalent.
 45. The tissue marker accordingto claim 40, wherein each of the plurality of elongate members passesthrough the body and extends from each of the first surface and thesecond surface.